Decreased T1 Contrast between Gray Matter and Normal-Appearing White Matter in CADASIL

BACKGROUND AND PURPOSE:CADASIL is the most frequent hereditary small-vessel disease of the brain. The clinical impact of various MR imaging markers has been repeatedly studied in this disorder, but alterations of contrast between gray matter and normal-appearing white matter remain unknown. The aim of this study was to evaluate the contrast alterations between gray matter and normal-appearing white matter on T1-weighted images in patients with CADASIL compared with healthy subjects.MATERIALS AND METHODS:Contrast between gray matter and normal-appearing white matter was assessed by using histogram analyses of 3D T1 high-resolution MR imaging in 23 patients with CADASIL at the initial stage of the disease (Mini-Mental State Examination score > 24 and modified Rankin scale score ≤ 1; mean age, 53.5 ± 11.1 years) and 30 age- and sex-matched controls.RESULTS:T1 contrast between gray matter and normal-appearing white matter was significantly reduced in patients compared with age- and sex-matched controls (patients: 1.35 ± 0.08 versus controls: 1.43 ± 0.04, P < 10⁻⁵). This reduction was mainly driven by a signal decrease in normal-appearing white matter. Contrast loss was strongly related to the volume of white matter hyperintensities.CONCLUSIONS:Conventional 3D T1 imaging shows significant loss of contrast between gray matter and normal-appearing white matter in CADASIL. This probably reflects tissue changes in normal-appearing white matter outside signal abnormalities on T2 or FLAIR sequences. These contrast alterations should be taken into account for image interpretation and postprocessing.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small-vessel disease of the brain secondary to mutations of the NOTCH3 gene.¹ Conventional MR imaging markers have been repeatedly investigated in this disorder.^2–5 The impact of lacunar lesions detected on T1-weighted sequences seems more important than that of white matter lesions observed on FLAIR sequences.⁶ Recently, various measures of brain and cortical atrophy were shown to be related to clinical worsening.^7,8As reported in the context of Alzheimer disease,⁹ contrast between gray matter and normal-appearing white matter (NAWM) may be altered in CADASIL. This could have important implications for both image interpretation in the clinical setting and postprocessing in research studies. So far however, the alterations of MR imaging T1 contrast between GM and NAWM have not been evaluated in CADASIL. The aim of the present study was to assess potential contrast alterations between GM and NAWM on T1-weighted images in patients with CADASIL at the initial stage of the disease compared with age- and sex-matched individuals.